Lobectomy Versus Sublobar Resection in Simultaneous Bilateral Thoracoscopic Lung Resection.

BACKGROUND: Simultaneous bilateral thoracoscopic lung resection (SBTLR) has been shown to be a feasible and efficacious approach for a wide range of pulmonary conditions. Our aim was to evaluate the impact of different procedures on surgical outcomes in patients receiving SBTLR. METHODS: Between 2012 and 2021, 207 patients with bilateral lung neoplasms who underwent SBTLR were retrospectively reviewed. Fifty-one patients received ipsilateral plus contralateral lobectomy or sublobectomy (lobar group), whilst 156 patients received bilateral sublobectomy (sublobar group). Propensity scores were calculated and matched. Perioperative and clinicopathologic outcomes were compared. RESULTS: The lobar group had a greater mean age (64.5 vs. 60.0 years, p = 0.008), longer operative time (254 vs. 205 min, p < 0.001), and more blood loss (74 vs. 46 ml, p < 0.001). The sublobar group had fewer complications (6.4 vs. 19.6%, p = 0.006), shorter hospital stay (4.8 vs. 7.4 days, p < 0.001), and lower hospital costs (p = 0.03). Among 50 pairs of matched groups, significant differences were found only in operative time, hospital stay, and costs. Maximum tumor size and pathological features differed significantly before and after matching (all p < 0.05), with the lobar group consistently demonstrating a larger main tumor (median, 2.5 cm) and a higher percentage of primary lung cancer (84%). Multivariate logistic regression analysis showed that a longer operative time was the factor associated with more complications (OR: 1.01; 95% CI 1.00-1.02, p = 0.002). CONCLUSIONS: With regard to SBTLR, our data suggests that sublobectomy may reduce the prolonged recovery, hospital costs, and complications incurred by lobectomy, without compromising oncological outcomes.

Ladinin 1 Shortens Survival via Promoting Proliferation and Enhancing Invasiveness in Lung Adenocarcinoma.

Lung cancer is one of the deadliest cancers worldwide, including in Taiwan. The poor prognosis of the advanced lung cancer lies in delayed diagnosis and non-druggable targets. It is worth paying more attention to these ongoing issues. Public databases and an in-house cohort were used for validation. The KM plotter was utilized to discover the clinical significance. GSEA and GSVA were adopted for a functional pathway survey. Molecular biological methods, including proliferation, migration, and the EMT methods, were used for verification. Based on public databases, the increased expression of Ladinin 1 (LAD1) was presented in tumor and metastatic sites. Furthermore, an in-house cohort revealed a higher intensity of LAD1 in tumor rather than in normal parts. The greater the expression of LAD1 was, the shorter the duration of lung adenocarcinoma (LUAD) patient survival. Moreover, the association of B3GNT3 with LAD1 affected the survival of LUAD patients. Functional analyses using GSEA and GSVA revealed the associations with survival, migration, invasion, and EMT. Biologic functions supported the roles of LAD1 in proliferation via the cell cycle and migration in EMT. This study reveals that LAD1 plays a major role in regulating proliferation and migration in lung cancer and impacts survival in LUAD. It is worth investing in further studies and in the development of drugs targeting LAD1.

Is a Chest Tube Necessary after Video-Assisted Thoracoscopic Mediastinal Tumor Resection?

BACKGROUND: The omission of chest tubes after thoracoscopic procedures such as sympathectomy, lung biopsy, and lung resection has proven efficacious in decreasing pain and length of hospital stay in some cases. However, its safety for mediastinal diseases remains unclear. This study evaluated the feasibility and outcome of eliminating chest drains after video-assisted thoracoscopic surgery (VATS) for mediastinal tumor resection. METHODS: We retrospectively investigated 70 patients receiving VATS mediastinal tumor resection in a single institution between January 2016 and November 2018. A total of 39 patients (drain group) received postoperative chest drains and 31 patients (no-drain group) did not. Group clinical outcomes and operation data were compared. A propensity score matching analysis was further performed to yield a fairer comparison. RESULTS: Before propensity score matching, the no-drain group had a higher prevalence of cystic lesions, a shorter operative time, and less blood loss compared with the drain group (p = 0.015, p = 0.018, and p < 0.001, respectively). After matching, the group differences in these perioperative variables lost significance (p = 0.095, 0.4, and 0.2, respectively). The no-drain group had lower postoperative day 2 pain scores and shorter postoperative hospital stays than the drain group, regardless of whether they were matched (pain: p = 0.028; hospital stay < 0.001) or not (pain: p = 0.003; hospital stay < 0.001). No major adverse events occurred in either group during hospitalization or follow-up period. CONCLUSION: Eliminating chest drain placement after VATS mediastinal tumor resection may benefit some patients and decrease postoperative pain and hospital stay without increasing complications or compromising patient safety.

Downregulated antisense lncRNA ENTPD3-AS1 contributes to the development of lung adenocarcinoma.

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of ENTPD3-AS1 (ENTPD3 Antisense RNA 1) in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of ENTPD3-AS1 on the expression of NR3C1 was validated by siRNA-based silencing. The effect of miR-421 on the modulation of NR3C1 was determined by miRNA mimics and inhibitors transfection. ENTPD3-AS1 was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating NR3C1 expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of NR3C1. Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of NR3C1 with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of ENTPD3-AS1 by siRNA transfection decreased the levels of NR3C1, supporting the ENTPD3-AS1/miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that ENTPD3-AS1 could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that ENTPD3-AS1 and its indirect target NR3C1 can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

Upregulated enhancer of rudimentary homolog promotes epithelial­mesenchymal transition and cancer cell migration in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the deadliest cancers regarding both mortality rate and number of deaths and warrants greater effort in the development of potential therapeutic targets. The enhancer of rudimentary homolog (ERH) has been implicated in the promotion and progression of certain types of cancer. In the present study, ERH was assessed for its expression pattern and survival association with LUAD in public transcriptomic and proteomic databases. Bioinformatic methods and data from websites, including University of Alabama at Birmingham CANcer data analysis Portal and The Cancer Genome Atlas, were utilized to demonstrate the functional behaviors and corresponding pathways of ERH in LUAD. Human A549 and CL1­0 cell lines were used to validate the findings via functional assays. It was demonstrated that the expression of ERH, at both the transcriptomic and proteomic levels, was higher in LUAD compared with in adjacent non­tumor lung tissue and was associated with worse survival prognosis. Moreover, high ERH expression was correlated with more aggressive functional states, such as cell cycle and invasion in LUAD, and the positive ERH­correlated gene set was associated with worse survival and an immunosuppressive tumor microenvironment. Small nuclear ribonucleoprotein polypeptide G was identified as a molecule that potentially interacted with ERH. Lastly, it was demonstrated that ERH promoted epithelial­mesenchymal transition and cell migration in vitro, but not proliferation. In conclusion, higher expression of ERH in LUAD may facilitate cancer progression and confer worse outcomes. Further deep investigation into the role of ERH in LUAD is needed.

Diastole/Body Mass Index Ratio Can Predict Post-Thoracoscopic Surgery Metastasis in Stage I Lung Adenocarcinoma.

BACKGROUND: According to recent animal models for lung adenocarcinoma metastasis, cardiac function may be related to the clinical outcome. The aim of this study is to identify a predictable index for postoperative metastasis (POM) that is associated with cardiac function. METHODS: Two hundred and seven consecutive patients who underwent thoracoscopic resection for stage I lung adenocarcinoma were included. Disease-free survival (DFS), overall survival (OS), and patients' clinical and pathological characteristics were analyzed. RESULTS: Among the 207 patients, 17 cases demonstrated metastasis, 110 cases received a preoperative echocardiogram, and six cases had POM. Mitral valve peak A velocity, which is one of the left ventricular diastolic function parameters affected by BMI (MVPABMI), was associated with a negative factor for POM (hazard ratio (HR): 2.139, p = 0.019) and a poor 5-year DFS in the above median (100% vs. 87%, p = 0.014). The predictable rate increased from 30.7% to 75% when the MVPABMI was above the median = 3.15 in the solid subtype). CONCLUSIONS: MVPABMI is a novel index for POM prediction in early-stage lung adenocarcinoma. This is a pilot study and the first attempt at research to verify that the diastole and the BMI may be associated with POM in early-stage lung adenocarcinoma.

Pneumorrhachis with spontaneous pneumomediastinum in pediatric patients: An 11-year retrospective study in Southern Taiwan.

BACKGROUND: Although uncommon, available evidence suggests that pneumorrhachis (PR) with spontaneous pneumomediastinum (SPM) in adulthood is usually benign and self-limiting. This study aimed to review our experience and identify the risk factors of PR in pediatric patients with SPM. METHODS: Between September 2007 and September 2017, SPM in patients aged ≤18 years was retrospectively reviewed and clinical features and outcomes between SPM patients with and without PR were analyzed. RESULTS: In total, thirty consecutive occurrences of SPM in 29 patients were finally identified and classified into SPM (n = 24) and SPM plus PR (n = 6) groups. No significant differences in received interventional exams, prophylactic antibiotic administration or restriction of oral intake between the two groups were found. Both groups were treated with hospitalization predominantly; but the SPM plus PR group tended to have longer length of hospital stay (median 5.5 vs. 3 days, p = 0.08). PR was observed more frequently in patients with abnormal serum C-reactive protein (CRP) levels (>5 mg/L), identified predisposing factors, and those with more severe grade of SPM (p = 0.005, 0.001 and < 0.001, respectively). On multivariable regression analysis, the SPM plus PR group exhibited more predisposing factors than did the SPM group (coefficient: 0.514, standard error: 0.136, p < 0.001). All patients were successfully treated without morbidity and mortality. CONCLUSION: Although patients with pneumorrhachis retained a higher CRP level, more identified predisposing factors and prolonged inpatient care, conservative management without an extensive work-up would be an appropriate and favorable strategy in pediatrics with concurrent SPM and PR.

Comparison of needlescopic and conventional video-assisted thoracic surgery for primary spontaneous pneumothorax.

Whether the outcome of primary spontaneous pneumothorax (PSP) when treated with needlescopic video-assisted thoracic surgery is positive is still under scrutiny. The present study was conducted to compare the needlescopic approach with the conventional approach. One-hundred and six patients with primary spontaneous pneumothorax who had undergone needlescopic video-assisted thoracic surgery (NVATS) between May 2006 and August 2008 were reviewed. Their age, gender, smoking status, BMI, side of attack, operative indications, operative time, intraoperative blood loss, postoperative length of stay, postoperative pain in visual analog scale (VAS), postoperative recurrence and follow-up period were recorded. These data were compared with those of 89 patients with PSP who had undergone conventional video-assisted thoracic surgery (CVATS) between June 2002 and April 2006. The operative time was shorter (NVATS: 82.36 ± 35.58 min, CVATS: 99.78 ± 35.74 min; p = 0.008) and intraoperative blood loss was less (NVATS: 16.67 ± 25.90 ml, CVATS: 24.36 ± 26.86 ml; p = 0.04) for the NVATS group. The postoperative pain in VAS was significantly less in NVATS. No major complication or mortality was found in either group. For treatment of primary spontaneous pneumothorax, NVATS is a safe and effective option. Further, it has the added benefit of less pain and improved cosmetics.

Pulmonary completion lobectomy after segmentectomy: An integrated analysis of perioperative outcomes.

BACKGROUND: Completion lobectomy (CL) after anatomical segmentectomy is technically challenging and rarely performed. Here, we aimed to report perioperative outcomes of a single center real-world CL data. METHODS: Seven patients who underwent CL after segmentectomy were retrospectively evaluated between 2015-2021. Additionally, 34 patients were included in the review based on relevant studies in the literature until March 2022. A total of 41 patients were finally analyzed and classified into groups, according to surgical approach (video-assisted thoracic surgery [VATS] and thoracotomy; 12 and 29 patients, respectively) or interval-to-CL following initial segmentectomy (≤8 weeks [short] and >8 weeks [long]; 11 and 30 patients, respectively). RESULTS: There were no significant differences in estimated blood loss, postoperative hospital stay, or complications between the predefined groups. However, a longer operative time was observed in the long interval-to-CL group than in the short interval-to-CL group (267 vs. 226 min, p = 0.02). The rate of severe hilar adhesions was higher in the thoracotomy versus VATS groups (72 vs. 42%, p = 0.06) and in the long versus short interval-to-CL groups (70 vs. 45%, p = 0.15). On multivariable logistic regression analysis of a subgroup (n = 30), completion lobectomy of upper lobes may be associated with severe hilar adhesions (p = 0.02, odds ratio: 13.98; 95% confidence interval [CI]: 1.36-143.71). CONCLUSION: Completion lobectomy after segmentectomy can be performed securely by either VATS or thoracotomy. Although the thoracotomy and long interval-to-CL groups retained a greater percentage of severe hilar adhesions, the perioperative outcomes were similar to those of VATS and short interval-to-CL groups, respectively.

Downregulated ADAMTS1 Incorporating A2M Contributes to Tumorigenesis and Alters Tumor Immune Microenvironment in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) still holds the most dreadful clinical outcomes worldwide. Despite advanced treatment strategies, there are still some unmet needs. Next-generation sequencing of large-scale cancer genomics discovery projects combined with bioinformatics provides the opportunity to take a step forward in meeting clinical conditions. Based on in-house and The Cancer Genome Atlas (TCGA) cohorts, the results showed decreased levels of ADAMTS1 conferred poor survival compared with normal parts. Gene set enrichment analyses (GSEA) indicated the negative correlation between ADAMTS1 and the potential roles of epithelial-mesenchymal transition (EMT), metastasis, and poor prognosis in LUAD patients. With the knockdown of ADAMTS1, A549 lung cancer cells exhibited more aggressive behaviors such as EMT and increased migration, resulting in cancer metastasis in a mouse model. The pathway interaction network disclosed the linkage of downregulated α2-macroglobulin (A2M), which regulates EMT and metastasis. Furthermore, immune components analysis indicated a positive relationship between ADAMTS1 and the infiltrating levels of multiple immune cells, especially anticancer CD4+ T cells in LUAD. Notably, ADAMTS1 expression was also inversely correlated with the accumulation of immunosuppressive myeloid-derived suppressor cells and regulatory T cells, implying the downregulated ADAMTS1 mediated immune adjustment to fit the tumor survival disadvantages in LUAD patients. In conclusion, our study indicates that ADAMTS1 interacts with A2M in regulating EMT and metastasis in LUAD. Additionally, ADAMTS1 contributes to poor prognosis and immune infiltration in LUAD patients.

The Therapeutic Potential of ADAMTS8 in Lung Adenocarcinoma without Targetable Therapy.

Lung cancer is well known for its high mortality worldwide. The treatment for advanced lung cancer needs more attention to improve its survival time. A disintegrin and metallopeptidase with thrombospondin motifs 8 (ADAMTS8) has been linked to several cancer types. However, its role in lung cancer is worthy of deep investigation to promote novel drug development. This study took advantage of RNA-seq and bioinformatics to verify the role that ADAMTS8 plays in lung cancer. The functional assays suggested that ADAMTS8 mediates invasion and metastasis when expressed at a low level, contributing to poor overall survival (OS). The expression of ADAMTS8 was under the regulation of GATA Binding Protein 1 (GATA1) and executed its pathologic role through Thrombospondin Type 1 Domain Containing 1 (THSD1) and ADAMTS Like 2 (ADAMTSL2). To define the impact of ADAMTS8 in the lung cancer treatment strategy, this study further grouped lung cancer patients in the TCGA database into mutated epidermal growth factor receptor (EGFR)/wild-type EGFR and programmed death ligand 1 (PD-L1) high/low groups. Importantly, the expression of ADAMTS8 was correlated positively with the recruitment of anticancer NKT cells and negatively with the infiltration of immunosuppressive Treg and exhausted T cells. The results indicated that lung cancer patients with higher ADAMTS8 levels among wild-type EGFR or low PD-L1 groups survive longer than those with lower levels do. This study indicates that ADAMTS8 might be a treatment option for patients with lung adenocarcinoma who lack efficient targeted or immunotherapies.

Characterization of the Oncogenic Potential of Eukaryotic Initiation Factor 4A1 in Lung Adenocarcinoma via Cell Cycle Regulation and Immune Microenvironment Reprogramming.

Lung adenocarcinoma (LUAD) is a common type of lung cancer. Although the diagnosis and treatment of LUAD have significantly improved in recent decades, the survival for advanced LUAD is still poor. It is necessary to identify more targets for developing potential agents against LUAD. This study explored the dysregulation of translation initiation factors, specifically eukaryotic initiation factors 4A1 (EIF4A1) and EIF4A2, in developing LUAD, as well as their underlying mechanisms. We found that the expression of EIF4A1, but not EIF4A2, was higher in tumor tissue and associated with poor clinical outcomes in LUAD patients. Elevated expression of EIF4H with poor prognosis may potentiate the oncogenic role of EIF4A1. Functional enrichment analysis revealed that upregulation of EIF4A1 was related to cell cycle regulation and DNA repair. The oncogenic effect of EIF4A1 was further elucidated by Gene Set Variation Analysis (GSVA). The GSVA score of the gene set positively correlated with EIF4A1 was higher in tumors and significantly associated with worse survival. In the meantime, gene set enrichment analysis (GSEA) also indicated that elevated EIF4A1 expression in LUAD patients was associated with a decreased infiltration score for immune cells by reducing anticancer immune cell types and recruiting immunosuppressive cells. Consistent with the results, the GSVA score of genes whose expression was negatively correlated with EIF4A1 was lower in the tumor tissue of LUAD cases with worse clinical outcomes and was strongly associated with the disequilibrium of anti-cancer immunity by recruiting anticancer immune cells. Based on the results from the present study, we hypothesize that the dysregulation of EIF4A1 might be involved in the pathophysiology of LUAD development by promoting cancer growth and changing the tumor immune microenvironment. This can be used to develop potential diagnostic biomarkers or therapeutic targets for LUAD.

Reduced tissue and serum resistin expression as a clinical marker for esophageal squamous cell carcinoma.

Esophageal cancer is one of the most common malignancies and leading cause of cancer-associated mortality worldwide. However, the molecular mechanisms underlying esophageal cancer progression and the development of clinical tools for effective diagnosis remain unclear. Resistin, which was originally identified as an adipose tissue-secretory factor, has been associated with obesity-related diseases, including certain types of cancer. Thus, the present study aimed to investigate the expression levels of resistin in tissue and serum specimens from patients with esophageal squamous cell carcinoma (ESCC) to determine the potential biological effects of resistin on ESCC cells. The results demonstrated that both tissue and serum resistin levels were significantly lower in patients with ESCC compared with healthy controls. In addition, resistin expression was positively associated with the body mass index of patients with ESCC. In vitro studies revealed that resistin inhibited the migratory ability of ESCC cells, while having no effect on ESCC cell proliferation. Taken together, these results suggest that resistin may have the potential to be developed into a clinical marker for ESCC. However, further studies are required to investigate resistin receptor expression and determine the potential involvement of resistin-associated biological pathways, which may provide insight for future development of targeted therapies for resistin-mediated ESCC.

Intragastric Botulinum Toxin A Injection Is an Effective Obesity Therapy for Patients with BMI > 40 kg/m2: a Systematic Review and Meta-analysis.

We conducted a systematic review and meta-analysis to assess the efficacy of intragastric BTA injection in patients with obesity and morbid obesity. Five RCTs were identified. Intragastric BTA injection was no superior to saline in absolute weight loss or BMI change, but significantly lengthened the gastric emptying time (MD, 15.57; 95% CI, 8.75 to 22.38). In meta-regression analysis, the absolute weight loss was lower in the patients with high baseline BMI. In subgroup analysis, the use of BTA in absolute weight loss was significantly lower among the patients with baseline BMI more than 40 kg/m2 (MD, - 5.31; 95% CI, - 6.17 to - 4.45). The benefit of intragastric BTA injection in reduction of absolute weight was observed in patients with baseline BMI more than 40 kg/m2.

Simultaneous bilateral thoracoscopic blebs excision reduces contralateral recurrence in patients undergoing operation for ipsilateral primary spontaneous pneumothorax.

OBJECTIVE: Contralateral recurrence in patients with primary spontaneous pneumothorax is approximately 15%. If positive for blebs, the recurrence rate increases to 26%. This study seeks to determine whether simultaneous contralateral video-assisted thoracic surgery blebs excision would effectively lower the contralateral incidence of pneumothorax in patients undergoing surgery for ipsilateral primary spontaneous pneumothorax. METHODS: Between January 2009 and December 2015, 335 patients with primary spontaneous pneumothorax, surgically treated in a single institution, were retrospectively studied. The median follow-up was 75 (50-99) months. All patients received video-assisted thoracic surgery blebectomy/bullectomy with pleural abrasions. They were classified into 3 groups: (1) ipsilateral video-assisted thoracic surgery without contralateral blebs/bullae included 142 patients with ipsilateral primary spontaneous pneumothorax without contralateral blebs/bullae only receiving ipsilateral video-assisted thoracic surgery; (2) ipsilateral video-assisted thoracic surgery with contralateral blebs/bullae included 123 patients with ipsilateral primary spontaneous pneumothorax with contralateral blebs/bullae receiving only ipsilateral video-assisted thoracic surgery; and (3) bilateral video-assisted thoracic surgery with contralateral blebs/bullae included 70 patients with ipsilateral primary spontaneous pneumothorax with contralateral blebs/bullae receiving 1-stage bilateral video-assisted thoracic surgery. Demographic data, perioperative details, recurrence patterns, recurrence-free survivals, and risk factors were compared. RESULTS: The percentage of contralateral recurrence for the ipsilateral video-assisted thoracic surgery without contralateral blebs/bullae, ipsilateral video-assisted thoracic surgery with contralateral blebs/bullae, and bilateral video-assisted thoracic surgery with contralateral blebs/bullae groups differed significantly (0.7%, 14.6%, and 2.9%, respectively; P = .002). Multivariate analysis using the Cox proportional hazard model revealed that age less than 18 years (hazard ratio, 2.71; 95% confidence interval, 1.14-6.44; P = .024) and ipsilateral video-assisted thoracic surgery with contralateral blebs/bullae (hazard ratio, 22.13, 95% confidence interval, 2.96-165, P = .003) were predictors of contralateral recurrence, of which recurrence-free survival was notably different among groups as determined by Kaplan-Meier analysis (P < .0001). CONCLUSIONS: Simultaneous contralateral blebectomy in patients with primary spontaneous pneumothorax receiving ipsilateral video-assisted thoracic surgery significantly lowered future contralateral recurrence.

Salvage surgery using simultaneous clamshell thoracotomy with median sternotomy for mediastinal growing teratoma syndrome.

This report describes the case of a 17-year-old man who developed mediastinal growing teratoma syndrome following two cycles of chemotherapy, after an initial diagnosis of primary mediastinal nonseminomatous germ cell tumor. The large, rapidly-growing mediastinal tumor was completely resected in conjunction with right pneumonectomy, using simultaneous clamshell thoracotomy and median sternotomy. The salvage surgery with perioperative management involved in mediastinal growing teratoma syndrome is presented here. KEY POINTS: Significant findings of the study The diagnosis and surgical management are challenging for patients with mediastinal growing teratoma syndrome. Nevertheless, with proper operative planning, favorable outcomes can be attained with complete resection despite the characteristic rapid growth and massive size of these neoplasms. What this study adds In spite of postoperative sternal dehiscence, we believe that a simultaneous clamshell thoracotomy with median sternotomy approach remains a viable option for an extremely large mediastinal growing teratoma, when tumor size prevents safe resection using other approaches due to limited visualization.

Expedite recovery from esophagectomy and reconstruction for esophageal squamous cell carcinoma after perioperative management protocol reinvention.

BACKGROUND: Surgery for esophageal cancer is invasive and challenging, and always to be followed with arduous post-operative care and recovery. This study, maybe one of the first in Asian populations, is to determine whether a reinvented protocol for perioperative management for esophageal cancer surgery which is being implemented in our department, will lead to a faster convalescence and also significantly decrease financial burdens garnered by patients during hospitalization. METHODS: Operated on by the same surgeon and team in the same hospital, consecutive patients who had received esophagectomy and reconstruction for esophageal squamous cell carcinoma were retrospectively reviewed. On the basis of two different treatment periods, patients were divided into two groups: A and B. Group A was patients who had received the new reinvented protocol between 2012 and 2016, while group B patients were those having received the previous protocol between 2008 and 2011. Their demographics, post-operative outcome, and hospital charges were collected and compared. RESULTS: There were 64 patients in group A, and 69 in group B. Ventilator days (P<0.001), ICU stay (P<0.001), and post-operative stay (P<0.001) were significantly shorter in group A patients. Complication rates were similar between the two groups. No hospital mortality was noted in either group. Hospital charges in group A were found to be perceptively lower, although not statistically significant (P value =0.078). CONCLUSIONS: The current protocol of perioperative care effectively ameliorated convalescence after esophagectomy and reconstruction for esophageal squamous cell carcinoma without increasing complication rate or mortality. It is also potentially more practical in future health care policies during this era of financial shortage.

Expression of redox sensing factor Nrf2 in lung macrophages and type II pneumocytes as a prognostic factor in pneumothorax recurrence.

BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common clinical problem. However, PSP recurrence is still a major concern. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a protective role against oxidative airway diseases. The aim was to investigate the role of Nrf2 in PSP patients and its correlation with recurrence. METHODS: Eighty-nine patients were enrolled and received wedge resection of lung with identifiable blebs. Nrf2 expression in resected lung tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables. The prognostic value of Nrf2 for incidence-of-recurrence was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. RESULTS: Nrf2 staining was predominantly observed in alveolar macrophages and type II pneumocytes of PSP patients and correlated with recurrence (P<0.001 and P=0.001, respectively) and PSP location (macrophages, P=0.013). High Nrf2 expression was correlated with better incidence-of-recurrence (macrophages, P=0.003; type II pneumocytes, P=0.003). Moreover, incidence-of-recurrence was better in patients with higher Nrf2 expression, especially those in the age ≤20, male, and non-smoking groups (macrophages, P=0.009, 0.006, and 0.012; type II pneumocytes, P=0.003, 0.011, and 0.010, respectively). CONCLUSIONS: High Nrf2 expression in alveolar macrophages and type II pneumocytes was significantly associated with the decreased recurrence risk and was the independent factor predicting a better incidence-of-recurrence in PSP. Our results suggest that Nrf2 activation in high risk patients may be a potential target for reducing PSP recurrence.

Laricitrin suppresses increased benzo(a)pyrene-induced lung tumor-associated monocyte-derived dendritic cell cancer progression.

Benzo(a)pyrene (BaP) stimulates lung cancer cells, promoting monocyte-derived dendritic cells to secrete soluble factors, including heparin binding-epidermal growth factor and C-X-C motif chemokine 5. The secretions from monocyte-derived dendritic cells stimulate the progression of lung cancer cells, including the migration and invasion of cells. To the best of our knowledge, these secretions remain unknown, and require additional study. The present study identified that treatment with BaP-H1395-tumor-associated dendritic cell-conditioned medium had the most marked effect on cell migration and invasion. This result may be associated with the female gender, stage 2 adenocarcinoma or mutation of the proto-oncogene B-Raf (BRAF), according to the cell line background. Laricitrin, a dietary flavonoid derivative present in grapes and red wine, suppresses certain factors and decreases the progression of lung cancer cells that are promoted by BaP in the lung cancer tumor microenvironment. The results of the present study suggest that prolonged exposure to BaP exacerbates lung cancer, particularly in female lung cancer patients with the BRAF mutation, but that laricitrin may ameliorate this effect.

Tricetin, a dietary flavonoid, suppresses benzo(a)pyrene­induced human non­small cell lung cancer bone metastasis.

This is the first study to demonstrate that benzo(a)-pyrene (BaP) was able to enhance the production of parathyroid hormone­related protein (PTHrP) by human non­small cell lung cancer H460 cells. Such effect would further contribute to bone metastasis of lung cancer by increasing osteoclastogenesis. This study is also the first to reveal that tricetin (TCN), a flavonoid derivative found in Myrtaceae pollen and Eucalyptus honey, was able to reverse BaP­mediated bone resorption activity of lung cancer cells. Human non­small cell lung cancer H460 cells were treated with BaP to generate conditioned medium. When osteoblasts were cultured with BaP­H460­CM, their expression of osteoclastogenesis activator macrophage colony­stimulating factor (M­CSF) and receptor activator of nuclear factor κB ligand (RANKL) was increased. BaP­H460­CM reduced the production of osteoprotegerin (OPG), an osteoclastogenesis inhibitor, in osteoblasts. Osteoclastogenesis and bone resorption activity of H460 cells were increased by BaP­H460­CM. With BaP­mediated PTHrP upregulation, IL­8 secretion in H460 cells was increased contributing to human non­small cell lung cancer­mediated osteoclast differentiation and bone resorption. Moreover, TCN suppressed BaP­mediated bone resorption. Therefore, TCN may be a novel agent for treatment of non­small cell lung cancer patients with bone metastasis.